Bronchial Artery Revascularization Improves Tracheal Anastomotic Healing after Lung Transplantation

The study aimed to clarify the role of direct bronchial artery revascularization (BAR) after en bloc double-lung (DLT) and heart-lung transplantation (HLT). Group I comprised eight patients with en bloc DLT or HLT and successful BAR, while group II included 14 DLT or HLT cases without BAR or with failed BAR. From these groups, 2 subgroups were extracted: group III, including 6 cases of en bloc DLT with successful BAR and group IV 10 HLT cases without or with failed BAR. Airway healing was evaluated at bronchoscopy and patency of BAR with angiography. Pulmonary viral, bacterial and fungal infections, rejections and bronchiolitis obliterans syndrome (BOS) were registered. Tracheal healing at 2 weeks and 3 months was better in group I than in group II (p = 0.003 and p = 0.05, respectively). Compared with group IV, tracheal anastomotic healing at 2 weeks was better in group III (p = 0.007) and tended to be better also after 3 months (p = 0.07). The incidence of infections, rejection or BOS did not differ between groups I and II. BAR thus improved healing of tracheal anastomosis.     

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study

PurposeLarge-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls.MethodsAqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography – tandem mass spectrometry (LFQ nLC-MS/MS). The severity of macular edema was measured as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Proteins were filtered by requiring quantification in at least 50% of the samples in each group without imputation of missing values. Significantly changed proteins were identified with a permutation-based calculation with a false discovery rate at 0.05.ResultsIn BRVO, 52 proteins were differentially expressed. Regulated proteins were involved in cell adhesion, coagulation, and acute-phase response. Apolipoprotein C-III, complement C3, complement C5, complement factor H, fibronectin, and fibrinogen chains were increased in BRVO and correlated with CRT. Fibronectin also correlated with best corrected visual acuity (BCVA) and vascular endothelial growth factor (VEGF). Monocyte differentiation antigen CD14 (CD14) and lipopolysaccharide-binding protein (LBP) were upregulated in BRVO. Contactin-1 and alpha-enolase were downregulated in BRVO and correlated negatively with CRT.ConclusionsMultiple proteins, including complement factors, fibrinogen chains, and apolipoprotein C-III, correlated with CRT, indicating a multifactorial response. Fibronectin correlated with BCVA, CRT, and VEGF. Fibronectin may reflect the severity of BRVO. The proinflammatory proteins CD14 and LBP were upregulated in BRVO.     

Electroencephalography and analgesics

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms ‘analgesics’, ‘electroencephalography’ and ‘evoked potentials’ for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients.     

In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children

P. falciparum-infected red blood cells (IRBC) can adhere to endothelial host receptors through parasite-encoded, clonally variant surface antigens (VSA). The VSA-mediated IRBC adhesion and the acquired VSA-specific antibody response have both been linked to IRBC organ tropism and disease severity. Parasites isolated from young children with severe malaria (SM) tend to express a limited and conserved set of VSA (VSASM) that are both stronger and more commonly recognized by IgG in the plasma of malaria-exposed individuals than VSA (VSAUM) expressed by parasites causing uncomplicated malaria (UM) in older semi-immune children. Establishment of the genetic mechanism underlying changes in VSA expression in response to in vitro selective pressure is now possible because of the availability of the entire genomic sequence of the P. falciparum clone 3D7. As a first step towards direct molecular identification of VSASM-encoding genes in 3D7, we report here a method of enforcing expression of VSASM-like antigens in this parasite clone by a novel selection method using plasma from semi-immune children with low VSAUM-specific, but high VSASM-specific, IgG reactivity. In addition to the resulting increase in VSA-specific IgG recognition, VSASM-expressing 3D7(3D7-Dodowa1) showed reduced adhesion to CD36. Finally, levels of IgG specific for the VSA expressed by 3D7-Dodowa1 were uniformly higher than those of IgG with specificity for VSA expressed by the unselected 3D7 in plasma samples from geographically and epidemiologically diverse areas of endemic parasite transmission. The described selection method appears a useful tool in the identification of genes encoding VSA involved in severe and life-threatening P. falciparum malaria.